Search results for: poor outcome of delayed breast cancer treatment

Authors: Roberta Martino, Viviana Ventre

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Intertemporal choices are choices under conditions of uncertainty in which the consequences are distributed over time. The Discounted Utility Model is the essential reference for describing the individual in the context of intertemporal choice. The model is based on the idea that the individual selects the alternative with the highest utility, which is calculated by multiplying the cardinal utility of the outcome, as if the reception were instantaneous, by the discount function that determines a decrease in the utility value according to how the actual reception of the outcome is far away from the moment the choice is made. Initially, the discount function was assumed to have an exponential trend, whose decrease over time is constant, in line with a profile of a rational investor described by classical economics. Instead, empirical evidence called for the formulation of alternative, hyperbolic models that better represented the actual actions of the investor. Attitudes that do not comply with the principles of classical rationality are termed anomalous, i.e., difficult to rationalize and describe through normative models. The development of behavioral finance, which describes investor behavior through cognitive psychology, has shown that deviations from rationality are due to the limited rationality condition of human beings. What this means is that when a choice is made in a very difficult and information-rich environment, the brain does a compromise job between the cognitive effort required and the selection of an alternative. Moreover, the evaluation and selection phase of the alternative, the collection and processing of information, are dynamics conditioned by systematic distortions of the decision-making process that are the behavioral biases involving the individual's emotional and cognitive system. In this paper we present an original decomposition of the discount function to investigate the psychological principles of hyperbolic discounting. It is possible to decompose the curve into two components: the first component is responsible for the smaller decrease in the outcome as time increases and is related to the individual's impatience; the second component relates to the change in the direction of the tangent vector to the curve and indicates how much the individual perceives the indeterminacy of the future indicating his or her aversion to uncertainty. This decomposition allows interesting conclusions to be drawn with respect to the concept of impatience and the emotional drives involved in decision-making. The contribution that neuroscience can make to decision theory and inter-temporal choice theory is vast as it would allow the description of the decision-making process as the relationship between the individual's emotional and cognitive factors. Neurofinance is a discipline that uses a multidisciplinary approach to investigate how the brain influences decision-making. Indeed, considering that the decision-making process is linked to the activity of the prefrontal cortex and amygdala, neurofinance can help determine the extent to which abnormal attitudes respect the principles of rationality.

Keywords: impatience, intertemporal choice, neurofinance, rationality, uncertainty

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Authors: Safaa S. Hassan, Mohammed H. Elbakry, Safwat A. Mangoura, Zainab M. Omar

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Background: Liver fibrosis is the main reason for increased mortality in chronic liver disease. It has no standard treatment. Antioxidants from a variety of sources are capable of slowing or preventing oxidation of other molecules. Aim: to evaluate the hepatoprotective effect of vit. C, vit. E and gallic acid in comparison to silymarin in the rat model of carbon tetrachloride induced liver fibrosis and their possible mechanisms of action. Material& Methods: A total number of 60 adult male albino rats 160-200gm were divided into six equal groups; received subcutaneous (s.c) injection for 8 weeks. Group I: as control. Group II: received 1.5 mL/kg of CCL4 .Group III: CCL4 and co- treatment with silymarin 100mg/kg p.o. daily. Group IV: CCL4 and co-treatment with vit. C 50mg/kg p.o. daily. Group V: CCL4 and co-treatment with vit. E 200mg/kg. p.o. Group VI: CCL4 and co-treatment with Gallic acid 100mg/kg. p.o. daily. Liver was processed for histological and immunohistochemical examination. Levels of AST, ALT, ALP, reduced GSH, MDA, SOD and hydroxyproline concentration were measured and evaluated statistically. Results: Light and electron microscopic examination of liver of group II exhibited foci of altered cells with dense nuclei and vacuolated, granular cytoplasm, mononuclear cell infiltration in portal areas, profuse collagen fiber deposits were found around portal tract, more intense staining α-SMA-positive cells occupied most of the liver fibrosis tissue, electron lucent areas in the cytoplasm of the hepatocytes, margination of nuclear chromatin. Treatment by any of the antioxidants variably reduced the hepatic structural changes induced by CCL4. Biochemical analysis showed that carbon tetrachloride significantly increased the levels of serum AST, ALT, ALP, hepatic malondialdehyde and hydroxyproline content. Moreover, it decreased the activities of superoxide dismutase and glutathione. Treatment with silymarin, gallic acid, vit. C and vit. E decreased significantly the AST, ALT, and ALP levels in plasma, MDA and hydroxyproline and increased the activities of SOD and glutathione in liver tissue. The effect of administration of CCl4 was improved with the used antioxidants in variable degrees. The most efficient antioxidant was silymarin followed by gallic acid and vit. C then vit. E. It is possibly due to their antioxidant effect, free radical scavenging properties and the reduction of oxidant dependent activation and proliferation of HSCs. Conclusion: So these antioxidants can be a promising drugs candidate for ameliorating liver fibrosis better than the use of the drugs and their side effects.

Keywords: antioxidant, ccl4, gallic acid, liver fibrosis

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Authors: Mathew Tran, Deepa Patel, Breann Prophete, Irandokht Khaki Najafabadi

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Status epilepticus is a neurological disorder requiring emergent control with medical therapy. Based on guideline recommendations for adults with status epilepticus, the first-line treatment is to start a benzodiazepine, as they are quick at seizure control. The second step is to initiate a non-benzodiazepine anti-epileptic drug to prevent refractory seizures. Studies show that the anti-epileptic drugs are approximately equivalent in status epilepticus control once a benzodiazepine has been given. This review provides a brief overview of the management of status epilepticus based on evidence from the literature and evidence-based guidelines.

Keywords: neurological disorder, seizure, status epilepticus, benzo diazepines, antiepileptic agents

Procedia PDF Downloads 114

Authors: Ricardo Alberto Chiong Zevallos, Eduardo Moraes Rego Reis

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Pancreatic adenocarcinoma (PDAC) patients have a less than 10% 5-year survival rate. PDAC has no defined diagnostic and prognostic biomarkers. Gemcitabine is the first-line drug in PDAC and several other cancers. Long non-coding RNAs (lncRNAs) contribute to the tumorigenesis and are potential biomarkers for PDAC. Although lncRNAs aren’t translated into proteins, they have important functions. LncRNAs can decoy or recruit proteins from the epigenetic machinery, act as microRNA sponges, participate in protein translocation through different cellular compartments, and even promote chemoresistance. The chromatin remodeling enzyme EZH2 is a histone methyltransferase that catalyzes the methylation of histone 3 at lysine 27, silencing local expression. EZH2 is ambivalent, it can also activate gene expression independently of its histone methyltransferase activity. EZH2 is overexpressed in several cancers and interacts with lncRNAs, being recruited to a specific locus. EZH2 can be recruited to activate an oncogene or silence a tumor suppressor. The lncRNAs misregulation in cancer can result in the differential recruitment of EZH2 and in a distinct epigenetic landscape, promoting chemoresistance. The relevance of the EZH2-lncRNAs interaction to chemoresistant PDAC was assessed by Real Time quantitative PCR (RT-qPCR) and RNA Immunoprecipitation (RIP) experiments with naïve and gemcitabine-resistant PDAC cells. The expression of several lncRNAs and EZH2 gene targets was evaluated contrasting naïve and resistant cells. Selection of candidate genes was made by bioinformatic analysis and literature curation. Indeed, the resistant cell line showed higher expression of chemoresistant-associated lncRNAs and protein coding genes. RIP detected lncRNAs interacting with EZH2 with varying intensity levels in the cell lines. During RIP, the nuclear fraction of the cells was incubated with an antibody for EZH2 and with magnetic beads. The RNA precipitated with the beads-antibody-EZH2 complex was isolated and reverse transcribed. The presence of candidate lncRNAs was detected by RT-qPCR, and the enrichment was calculated relative to INPUT (total lysate control sample collected before RIP). The enrichment levels varied across the several lncRNAs and cell lines. The EZH2-lncRNA interaction might be responsible for the regulation of chemoresistance-associated genes in multiple cancers. The relevance of the lncRNA-EZH2 interaction to PDAC was assessed by siRNA knockdown of a lncRNA, followed by the analysis of the EZH2 target expression by RT-qPCR. The chromatin immunoprecipitation (ChIP) of EZH2 and H3K27me3 followed by RT-qPCR with primers for EZH2 targets also assess the specificity of the EZH2 recruitment by the lncRNA. This is the first report of the interaction of EZH2 and lncRNAs HOTTIP and PVT1 in chemoresistant PDAC. HOTTIP and PVT1 were described as promoting chemoresistance in several cancers, but the role of EZH2 is not clarified. For the first time, the lncRNA LINC01133 was detected in a chemoresistant cancer. The interaction of EZH2 with LINC02577, LINC00920, LINC00941, and LINC01559 have never been reported in any context. The novel lncRNAs-EZH2 interactions regulate chemoresistant-associated genes in PDAC and might be relevant to other cancers. Therapies targeting EZH2 alone weren’t successful, and a combinatorial approach also targeting the lncRNAs interacting with it might be key to overcome chemoresistance in several cancers.

Keywords: epigenetics, chemoresistance, long non-coding RNAs, pancreatic cancer, histone modification

Procedia PDF Downloads 91

Authors: Fitim Sadiku, Mjellma Rexhepi, Kreshnik Grezda, Jonijana Sadiku Tigani, Merita Qorolli, Blerta Rexhepi-Kelmendi, Zelie Sadiku, Laura Cakolli

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Background: According to the European Alliance of Associations for Rheumatology (EULAR), biologics should be considered alongside traditional treatments in Ankylosing Spondylitis (AS) patients with persistently high disease activity that directly affects functional capacity. Unfortunately, Kosovo’s health system only offers continuous treatment with etanercept (ETN), and most of the patients with AS are referred to be treated with this biological substance. Objectives: This study aims to explore the relationship between comorbidity, disease activity, and functional capacity in AS patients undergoing ETN treatment in Kosovo. Methods: In this cross-sectional study, we included patients diagnosed with AS who were being treated with ETN 50mg per week for at least 6 months at the Rheumatology Clinic of the University Clinical Center of Kosovo. Patients under 18, pregnant women, and patients with spinal fractures were excluded. This study was approved by the Ethics Committee of the Faculty of Medicine, University of Prishtina and a consent form was signed by patients for participating in the study. We collected data (September-December 2023) about socio-demographics and disease history. Moreover, the presence of comorbidities was measured by the Comorbidity Charlson Index; the disease activity was measured by the Ankylosing Spondylitis Disease Activity Score (ASDAS), and the functional capacity was measured by the Bath Ankylosing Spondylitis Functional Index (BASFI). Results: A total of 31 out of the 39 patients with AS receiving etanercept were included aged 18 to above 65 years (M= 40 years, SD= 14.39), and 87% were male. Diagnose delay was, on average, 7 years from the first symptoms (min-max= 0-24), while the disease duration on average was 7.5 years (min-max= 1- 50). Treatment duration with etanercept was from 0.5 to 6 years. The results indicate a significant positive correlation between comorbidity and BASFI (r= .615, p= .01) and disease activity. Additionally, a significant positive correlation exists between disease activity and BASFI (r= .507, p= .004). Regression analysis highlights the significance of both comorbidity and disease activity as predictors of patients’ functional capacity F (1, 29) = 10.047, p= .05 and F(1, 29) = 17.678, p= .01. No notable gender differences were observed. The study found no significant variations in comorbidity, disease activity, and functional capacity concerning the duration of ETN treatment. Conclusion: We found that in Kosovo, it takes at least 7 years for individuals to be diagnosed with AS from the first-time symptoms are experienced. This study showed that there is a positive correlation between comorbidity and functional capacity, disease activity and functional capacity in patients with AS undergoing etanercept treatment. Furthermore, results showed that comorbidity and disease activity are predictors of the functional status of the patients with AS receiving ETN. Gender and treatment duration with etanercept did not show any significant variations in these patients.

Keywords: ankylosing spondilitis, etanercept, physical wellbeing, comorbidities

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Authors: G. Battistoni, F. Collamati, E. De Lucia, R. Faccini, C. Mancini-Terracciano, M. Marafini, I. Mattei, S. Muraro, V. Patera, A. Sarti, A. Sciubba, E. Solfaroli Camillocci, M. Toppi, G. Traini, S. M. Valle, C. Voena

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Accelerated charged particles, mainly protons and carbon ions, are presently used in Particle Therapy (PT) to treat solid tumors. The precision of PT exploiting the charged particle high localized dose deposition in tissues and biological effectiveness in killing cancer cells demands for an online dose monitoring technique, crucial to improve the quality assurance of treatments: possible patient mis-positionings and biological changes with respect to the CT scan could negatively affect the therapy outcome. In PT the beam range confined in the irradiated target can be monitored thanks to the secondary radiation produced by the interaction of the projectiles with the patient tissue. The Dose Profiler (DP) is a novel device designed to track charged secondary particles and reconstruct their longitudinal emission distribution, correlated to the Bragg peak position. The feasibility of this approach has been demonstrated by dedicated experimental measurements. The DP has been developed in the framework of the INSIDE project, MIUR, INFN and Centro Fermi, Museo Storico della Fisica e Centro Studi e Ricerche 'E. Fermi', Roma, Italy and will be tested at the Proton Therapy center of Trento (Italy) within the end of 2017. The DP combines a tracker, made of six layers of two-view scintillating fibers with square cross section (0.5 x 0.5 mm2) with two layers of two-view scintillating bars (section 12.0 x 0.6 mm2). The electronic readout is performed by silicon photomultipliers. The sensitive area of the tracking planes is 20 x 20 cm2. To optimize the detector layout, a Monte Carlo (MC) simulation based on the FLUKA code has been developed. The complete DP geometry and the track reconstruction code have been fully implemented in the MC. In this contribution, the DP hardware will be described. The expected detector performance computed using a dedicated simulation of a 220 MeV/u carbon ion beam impinging on a PMMA target will be presented, and the result will be discussed in the standard clinical application framework. A possible procedure for real-time beam range monitoring is proposed, following the expectations in actual clinical operation.

Keywords: online range monitoring, particle therapy, quality assurance, tracking detector

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Authors: Hanan Algarni

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Background: Impairment of walking and balance skills has negative impact on functional independence and community participation after stroke. Gait recovery is considered a primary goal in rehabilitation by both patients and physiotherapists. Treadmill training coupled with virtual reality technology is a new emerging approach that offers patients with feedback, open and random skills practice while walking and interacting with virtual environmental scenes. Objectives: To synthesize the evidence around the effects of the VR treadmill training on gait speed and balance primarily, functional independence and community participation secondarily in stroke patients. Methods: Systematic review was conducted; search strategy included electronic data bases: MEDLINE, AMED, Cochrane, CINAHL, EMBASE, PEDro, Web of Science, and unpublished literature. Inclusion criteria: Participant: adult >18 years, stroke, ambulatory, without severe visual or cognitive impartments. Intervention: VR treadmill training alone or with physiotherapy. Comparator: any other interventions. Outcomes: gait speed, balance, function, community participation. Characteristics of included studies were extracted for analysis. Risk of bias assessment was performed using Cochrane's ROB tool. Narrative synthesis of findings was undertaken and summary of findings in each outcome was reported using GRADEpro. Results: Four studies were included involving 84 stroke participants with chronic hemiparesis. Interventions intensity ranged (6-12 sessions, 20 minutes-1 hour/session). Three studies investigated the effects on gait speed and balance. 2 studies investigated functional outcomes and one study assessed community participation. ROB assessment showed 50% unclear risk of selection bias and 25% of unclear risk of detection bias across the studies. Heterogeneity was identified in the intervention effects at post training and follow up. Outcome measures, training intensity and durations also varied across the studies, grade of evidence was low for balance, moderate for speed and function outcomes, and high for community participation. However, it is important to note that grading was done on few numbers of studies in each outcome. Conclusions: The summary of findings suggests positive and statistically significant effects (p<0.05) of VR treadmill training compared to other interventions on gait speed, dynamic balance skills, function and participation directly after training. However, the effects were not sustained at follow up in two studies (2 weeks-1 month) and other studies did not perform follow up measurements. More RCTs with larger sample sizes and higher methodological quality are required to examine the long term effects of VR treadmill effects on function independence and community participation after stroke, in order to draw conclusions and produce stronger robust evidence.

Keywords: virtual reality, treadmill, stroke, gait rehabilitation

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Authors: Prangya Ranjan Rout, Puspendu Bhunia, Rajesh Roshan Dash

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In a developing country like India, providing reliable and affordable wastewater treatment facilities in rural areas is a huge challenge. With the aim of enhancing the nutrient removal from rural domestic wastewater while reducing the cost of treatment process, a novel, integrated treatment system consisting of a multistage bio-filter with drop aeration and a post positioned attached growth carbonaceous denitrifying-bioreactor was designed and developed in this work. The bio-filter was packed with ‘dolochar’, a sponge iron industry waste, as an adsorbent mainly for phosphate removal through physiochemical approach. The Denitrifying bio-reactor was packed with many waste organic solid substances (WOSS) as carbon sources and substrates for biomass attachment, mainly to remove nitrate in biological denitrification process. The performance of the modular system, treating real domestic wastewater was monitored for a period of about 60 days and the average removal efficiencies during the period were as follows: phosphate, 97.37%; nitrate, 85.91%, ammonia, 87.85%, with mean final effluent concentration of 0.73, 9.86, and 9.46 mg/L, respectively. The multistage bio-filter played an important role in ammonium oxidation and phosphate adsorption. The multilevel drop aeration with increasing oxygenation, and the special media used, consisting of certain oxides were likely beneficial for nitrification and phosphorus removal, respectively, whereas the nitrate was effectively reduced by biological denitrification in the carbonaceous bioreactor. This treatment system would allow multipurpose reuse of the final effluent. Moreover, the saturated dolochar can be used as nutrient suppliers in agricultural practices and the partially degraded carbonaceous substances can be subjected to composting, and subsequently used as an organic fertilizer. Thus, the system displays immense potential for treating domestic wastewater significantly decreasing the concentrations of nutrients and more importantly, facilitating the conversion of the waste materials into usable ones.

Keywords: nutrient removal, denitrifying bioreactor, multi-stage bio-filter, dolochar, waste organic solid substances

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Authors: Abubakar Ibrahim Usman, Mustapha Halilu

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The provisions of rights to women in Islam have generated and are creating a tense and serious debate among Muslims and non-Muslims alike. The Muslims are arguing that Islam provides right to Womenfolk, but their actions, cultural/traditional practices, and treatment reveal otherwise, Non-Muslims, on the other hand, held a different view, saying that Islam has never made such provision. One may not blame their misconception, due to the wide spectrum of treatment given to women in many Muslim societies, which generated, fueled and geared the misconceptions and ceaseless barrage of sensational articles, movies and negative portrayal of Islam today. It has to put in our minds, many actions and Crimes of some Muslims (Who are mostly minority) did not represent the teachings and precepts of Islam, just like one cannot put blame on the parents of a child whose actions fall short of his home background.

Keywords: Islam, women rights, cultural practices, religion

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Authors: Mustapha Babatunde, Bassam Tawabini, Ole John Nielson

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Air dispersion (AD) models such as AERMOD are important tools for estimating the environmental impacts of air pollutant emissions into the atmosphere from anthropogenic sources. The outcome of these models is significantly linked to the climate condition like air temperature, which is expected to differ in the future due to the global warming phenomenon. With projections from scientific sources of impending changes to the future climate of Saudi Arabia, especially anticipated temperature rise, there is a potential direct impact on the dispersion patterns of air pollutants results from AD models. To our knowledge, no similar studies were carried out in Saudi Arabia to investigate such impact. Therefore, this research investigates the effects of climate temperature change on air quality in the Dammam Metropolitan area, Saudi Arabia, using AERMOD coupled with Station data using Sulphur dioxide (SO₂) – as a model air pollutant. The research uses AERMOD model to predict the SO₂ dispersion trends in the surrounding area. Emissions from five (5) industrial stacks on twenty-eight (28) receptors in the study area were considered for the climate period (2010-2019) and future period of mid-century (2040-2060) under different scenarios of elevated temperature profiles (+1ᵒC, + 3ᵒC and + 5ᵒC) across averaging time periods of 1hr, 4hr and 8hr. Results showed that levels of SO₂ at the receiving sites under current and simulated future climactic condition fall within the allowable limit of WHO and KSA air quality standards. Results also revealed that the projected rise in temperature would only have mild increment on the SO₂ concentration levels. The average increase of SO₂ levels was 0.04%, 0.14%, and 0.23% due to the temperature increase of 1, 3, and 5 degrees, respectively. In conclusion, the outcome of this work elucidates the degree of the effects of global warming and climate changes phenomena on air quality and can help the policymakers in their decision-making, given the significant health challenges associated with ambient air pollution in Saudi Arabia.

Keywords: air quality, sulfur dioxide, dispersion models, global warming, KSA

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Authors: Zemmouri Hassiba, Lounici Hakim, Mameri Nabil

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Dried crushed seeds of Moringa oleifera contain an effective soluble protein; a natural cationic polyelectrolyte which causes coagulation. The present study aims to investigate the performance of Moringa oleifera seed extract as natural coagulant in clarification of secondary wastewater treatment highly charged in colloidal. A series of Jar tests was undertaken using raw wastewater providing from secondary decanter of Reghaia municipal wastewater treatment plant (MWWTP) located in East of Algiers, Algeria. Coagulation flocculation performance of Moringa oleifera was evaluated through supernatant residual turbidity. Various influence parameters namely Moringa oleifera dosage and pH have been considered. Tests on Reghaia wastewater, having 129 NTU of initial turbidity, showed a removal of 69.45% of residual turbidity with only 1.5 mg/l of Moringa oleifera. This sufficient removal capability encourages the use of this bioflocculant for treatment of turbid waters. Based on this result, the coagulant seed extract of Moringa oleifera is better suited to clarify municipal wastewater by removing turbidity. Indeed, Moringa oleifera which is a natural resource available locally (South of Algeria) coupled to the non-toxicity, biocompatibility and biodegradability, may be a very interesting alternative to the conventional coagulants used so far.

Keywords: coagulation flocculation, colloids, moringa oleifera, secondary wastewater

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Authors: Jianwen Li, Hongfang Ma, Weixin Qian, Haitao Zhang, Weiyong Ying

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Methanol-to-propylene conversion was carried out in a continuous-flow fixed-bed reactor over nano-sized HZSM-5 zeolites. The HZSM-5 catalysts were synthesized with different Si/Al ratio and silicon sources, and treated with NaOH. The structural property, morphology, and acidity of catalysts were measured by XRD, N₂ adsorption, FE-SEM, TEM, and NH₃-TPD. The results indicate that the increment of Si/Al ratio decreased the acidity of catalysts and then improved propylene selectivity, while silicon sources had slight impact on the acidity but affected the product distribution. The desilication after alkali treatment could increase intracrystalline mesopores and enhance propylene selectivity.

Keywords: alkali treatment, HZSM-5, methanol-to-propylene, synthesis condition

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Authors: Sylwia K. Naliwajko, Justyna Moskwa, Patryk Nowakowski, Renata Markiewicz-Zukowska, Krystyna Gromkowska-Kepka, Anna Puscion-Jakubik, Maria H. Borawska

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Amygdalin is found in many fruit seeds, including apricot, peach, quince, apples, and almonds. Amygdalin (also named vitamin B17), as well as its sources, are commonly used as an alternative therapy or prevention of cancer. The potential activity of amygdalin is related to its enzymatic degradation to the hydrogen cyanide. Hydrogen cyanide is a toxic substance that causes liver and nerves damage, fever, coma or even death. Amygdalin is much better tolerated after intravenous than oral administration. The aim of this study was to examine the influence of amygdalin on glioblastoma multiforme cell lines. Three glioblastoma multiforme cell lines – U87MG, T98, LN18 were incubated (48 h) with amygdalin in concentrations 100, 250, 500, 1000 and 2000 µg/mL. The MTT (Thiazolyl Blue Tetrazolium Bromide) test and DNA binding test by [3H]-thymidine incorporation were used to determine the anti-proliferative activity of amygdalin. The secretion of metalloproteinases (MMP2 and MMP-9) from U87MG cells was estimated by gelatin zymography. The statistical analysis was performed using Statistica v. 13.0 software. The data was presented as a % of control. Amygdalin did not show significant inhibition of viability of all the glioblastoma cells in concentrations 100, 250, 500, 1000 µg/mL. In 2000 µg/mL there were significant differences compared to the control, but inhibition of viability was less than 20% (more than 80% of control). The average viability of U87MG cells was 92,0±4%, T98G: 85,8±3% and LN18: 94,7±2% of the control. There was no dose-response viability, and IC50 value was not recognized. DNA binding in U87MG cells was not inhibited (109,0±3 % of control). After treatment with amygdalin, we observed significantly increased secretion of MMP2 and MMP9 in U87MG cells (130,3±14% and 112,0±5% of control, respectively). Our results suggest that amygdalin has no anticancer activity in glioblastoma cell lines.

Keywords: amygdalin, anticancer, cell line, glioblastoma

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Authors: Chu Wan-Loy, Kok Yih-Yih, Choong Siew-Ling

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The human health risks due to poor air quality caused by a wide array of microorganisms have attracted much interest. Airborne algae have been reported as early as 19th century and they can be found in the air of tropic and warm atmospheres. Airborne algae normally originate from water surfaces, soil, trees, buildings and rock surfaces. It is estimated that at least 2880 algal cells are inhaled per day by human. However, there are relatively little data published on airborne algae and its related adverse health effects except sporadic reports of algae associated clinical allergenicity. A collection of airborne algae cultures has been established following a recent survey on the occurrence of airborne algae in indoor and outdoor environments in Kuala Lumpur. The aim of this study was to investigate the allergenic potential of the isolated airborne green and blue-green algae, namely Scenedesmus sp., Cylindrospermum sp. and Hapalosiphon sp.. The suspensions of freeze-dried airborne algae were adminstered into balb-c mice model through intra-nasal route to determine their allergenic potential. Results showed that Scenedesmus sp. (1 mg/mL) increased the systemic Ig E levels in mice by 3-8 fold compared to pre-treatment. On the other hand, Cylindrospermum sp. and Hapalosiphon sp. at similar concentration caused the Ig E to increase by 2-4 fold. The potential of airborne algae causing Ig E mediated type 1 hypersensitivity was elucidated using other immunological markers such as cytokine interleukin (IL)- 4, 5, 6 and interferon-ɣ. When we compared the amount of interleukins in mouse serum between day 0 and day 53 (day of sacrifice), Hapalosiphon sp. (1mg/mL) increased the expression of IL4 and 6 by 8 fold while the Cylindrospermum sp. (1mg/mL) increased the expression of IL4 and IFɣ by 8 and 2 fold respectively. In conclusion, repeated exposure to the three selected airborne algae may stimulate the immune response and generate Ig E in a mouse model.

Keywords: airborne algae, respiratory, allergenic, immune response, Malaysia

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Authors: Su-Ning Wang, Yao-Qiang Chen

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The CeO2-ZrO2-La2O3-Al2O3 composite oxides are synthesized using co-precipitation method by two different reactors (i.e. continuous stirred-tank reactor and batch reactor), and the corresponding Rh-only three-way catalysts are obtained by wet-impregnation approach. The textural, structural, morphology and redox properties of the support materials, as well as the catalytic performance of the Rh-only catalyst are investigated systematically. The results reveal that the materials (CZLA-C) synthesized by continuous stirred-tank reactor have a better physic-chemical properties than the counterpart material (CZLA-B) prepared by batch reactor. After aging treatment at 1000 ℃ for 5 h, the BET surface area and pore volume of S1 reach up to 76 m2 g-1 and 0.36 mL/g, respectively, which is higher than that of S2. The XRD and Raman results demonstrate that a high structural stability is obtained by S1 because of the negligible lattice variation and the slight grain growth after aging treatment. The SEM and TEM images display that the morphology of S1 is assembled by many homogeneous primary nanoparticles (about 6.12 nm) that are connected to form mesoporous structure The TPR measurement shows that S1 possesses a higher reduction ability than S2. Compared with the catalyst supported on the CZLA-B, the as-prepared CZLA-C demonstrates an improved three-way catalytic activity both before and after aging treatment.

Keywords: composite oxides, reactor, catalysis, catalytic performance

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Authors: Yang Wei, Xueyan Wang, Hui Zou

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Objective: Investigation the prevalence of menopausal symptoms in patients with allergic symptoms, evaluation of the effect of sex hormones combined with anti-allergic therapy in these patients. Method: Age of 45-65 years old women with allergic symptoms at the same time in gynecological-endocrinology clinic in our hospital were selected from Feb 1 to May 31, 2010, randomly. The patients were given oral estradiol valerate plus progestin pills combined with anti-allergy treatment and then evaluated twice a week and one month later. Evaluation criterion: Menopause Rating Scale (MRS) and the degree of clinical symptoms were used to evaluate menopause and allergy separately. Results: 1) There were 195 cases of patients with menopausal symptoms at the age. Their MRS were all over 15. 2) Among them 45 patients were with allergic symptom accounted for 23% which were diagnosed by allergic department. 3) Evaluated after one week: the menopausal symptoms were improved and MRS were less than or equal to 5 in all these patients; the skin symptom of allergic symptoms vanished completely. 4) Evaluated after one month: Menopause symptoms were improved steadily; other clinical symptoms of allergy were also improved or without recurrence. Conclusion: The incidence rate of menopausal women with clinical symptoms of allergic diseases is high and it needs attention. The effect of sex hormones combined with anti-allergic therapy is obvious.

Keywords: menopausal, allergy, sex hormone, anti-allergy treatment

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Authors: Claire B. Salvedia, Enrico P. Supangco, Francisco B. Eligado, Renato Sa Vega, Antonio A. Rayos

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The study was conducted to evaluate the effect of probiotic feeding on weight gain, blood biochemical and hematological indices of crossbred dairy goat kids. Sixteen (16) crossbred Anglo-Nubian x Saanen dairy goat kids, 3 to 4 months old, ranging from 19 to 23kg were randomly assigned into four treatments fed with 5x109 cfu/ml probiotic supplements; Treatment 1 – control; Treatment 2 – lactic acid bacteria (L. plantarum BS and P. acidilactici 3G3); treatment 3 – S. cerevisiae 2030; Treatment 4 – multi-strain probiotics (L. plantarum BS, P. acidilactici 3G3, and S.cerevisiae 2030). Feed ration provided daily for each of the experimental animals were composed of 1kg mixed concentrate feed ((Leucaena leucocephala dried leaves and pollard), and 4 kg fresh Pennisetum purpureum and Gliciridia sepium leaves (50:50). The experimental feeding trial lasted for 9 weeks. Result revealed that treatments fed with probiotics had significantly (P≤0.05) higher weight gain compared to the control. Significant effect on plasma urea nitrogen (PUN) and triglyceride were noted during 30th and 60th day of probiotic feeding. White blood cell counts were significantly affected by probiotic feeding during the 60th day. Concentrations of glucose and cholesterol remained unchanged throughout the experimental period. The findings suggests, under the condition of the experiment, that live probiotic feeding could have a significant role in improving weight gain and metabolism of crossbred dairy goat kids.

Keywords: probiotics, weight gain, blood biochemical indices, crossbred dairy goat kids

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Authors: Laura Bellassen, Idit Shachar

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Multiple sclerosis (MS) is a chronic neurological disorder characterized by demyelination of the central nervous system (CNS), leading to a wide range of physical and cognitive impairments. Myeloid cells in the CNS, such microglia and border associated macrophage cells, participate in the neuroinflammation in MS. Activation of those cells in MS contributes to the inflammatory response in the CNS and recruitment of immune cells in the this compartment. SLAMF5 is a cell surface receptor that functions as a homophilic adhesion molecule, whose signaling can activate or inhibit leukocyte function. In the current study we followed the expression and function of SLAMF5 in myeloid cells in the CNS and in the periphery in the murine model for MS, the experimental autoimmune encephalomyelitis model (EAE). Our results show that SLAMF5 deficiency or blocking decreases the expression of activation molecules and costimulatory molecules such as MHCII and CD80, resulting in delayed onset and reduced progression of the disease. Moreover, blocking SLAMF5 in peripheral monocytes derived from MS patients and iPSC-derived microglia cells, controls the expression of HLA-DR and CD80. Thus, SLAMF5 is a regulator of myeloid cells function and can serve as a therapeutic target in autoimmune disorders as Multiple Sclerosis.

Keywords: multiple sclerosis, EAE model, myeloid cells, new antibody, neuroimmunology

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Authors: Mustapha Babatunde, Bassam Tawabini, Ole John Nielson

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Air dispersion (AD) models such as AERMOD are important tools for estimating the environmental impacts of air pollutant emissions into the atmosphere from anthropogenic sources. The outcome of these models is significantly linked to the climate condition like air temperature, which is expected to differ in the future due to the global warming phenomenon. With projections from scientific sources of impending changes to the future climate of Saudi Arabia, especially anticipated temperature rise, there is a potential direct impact on the dispersion patterns of air pollutants results from AD models. To our knowledge, no similar studies were carried out in Saudi Arabia to investigate such impact. Therefore, this research investigates the effects of climate temperature change on air quality in the Dammam Metropolitan area, Saudi Arabia, using AERMOD coupled with Station data using Sulphur dioxide (SO2) – as a model air pollutant. The research uses AERMOD model to predict the SO2 dispersion trends on the surrounding area. Emissions from five (5) industrial stacks, on twenty-eight (28) receptors in the study area were considered for the climate period (2010-2019) and future period of mid-century (2040-2060) under different scenarios of elevated temperature profiles (+1oC, + 3oC and + 5oC) across averaging time periods of 1hr, 4hr and 8hr. Results showed that levels of SO2 at the receiving sites under current and simulated future climactic condition fall within the allowable limit of WHO and KSA air quality standards. Results also revealed that the projected rise in temperature would only have mild increment on the SO2 concentration levels. The average increase of SO2 levels were 0.04%, 0.14%, and 0.23% due to the temperature increase of 1, 3, and 5 degrees respectively. In conclusion, the outcome of this work elucidates the degree of the effects of global warming and climate changes phenomena on air quality and can help the policymakers in their decision-making, given the significant health challenges associated with ambient air pollution in Saudi Arabia.

Keywords: air quality, sulphur dioxide, global warming, air dispersion model

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Authors: Urarat Nanna, Jarinyaporn Naowaboot

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Tiliacora triandra (T. triandra) is traditional Southeast Asian medicine and widely used in the cuisines of northeast Thailand and Laos. It has been used as antipyretic, detoxication agent, antiinflammation. But the activity of T. triandra leaf water extract (TTW) in the regulation of metabolic syndrome is still little known. In this study, we evaluated the effects of TTW in high-fat diet (HFD)-induced obese mice. Male ICR mice were induced to be obese by HFD feeding (45 kcal% lard fat) for 12 weeks. During the last 6 weeks of diet feeding, the obese mice were treated with TTW at 250 and 500 mg/kg/day. The biochemical parameters and histology analysis were measured at the end of treatment period. After 6 weeks of TTW treatment, the hyperglycemia, hyperinsulinemia, hyperleptinemia and hyperlipidemia were significantly decreased. Hepatic lipid accumulation and adipocyte hypertrophy were also reduced. Serum adiponectin was increased in TTW-treated obese mice. TTW treatment could reduce the malondialdehyde in serum and liver tissue. Furthermore, the elevated serum inflammatory cytokines, tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 were reduced (MCP-1) by TTW. These results suggest that T. triandra leaf is a beneficial plant in alleviating hyperglycemia, hyperlipidemia, oxidative stress and inflammation in the obese condition induced by HFD.

Keywords: Tiliacora triandra, insulin resistance, hyperlipidemia, oxidative stress

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Authors: Nabil Al-Zaqri

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Semiconductor photocatalysts with surface defects display incredible light absorption bandwidth, and these defects function as highly active sites for oxidation processes by interacting with the surface band structure. Accordingly, engineering the photocatalyst with surface oxygen vacancies will enhance the semiconductor nanostructure's photocatalytic efficiency. Herein, a CeO2₋ₓ nanostructure is designed under the influence of low-frequency ultrasonic waves to create surface oxygen vacancies. This approach enhances the photocatalytic efficiency compared to many heterostructures while keeping the intrinsiccrystal structure intact. Ultrasonic waves induce the acoustic cavitation effect leading to the dissemination of active elements on the surface, which results in vacancy formation in conjunction with larger surface area and smaller particle size. The structural analysis of CeO₂₋ₓ revealed higher crystallinity, as well as morphological optimization, and the presence of oxygen vacancies is verified through Raman, X-rayphotoelectron spectroscopy, temperature-programmed reduction, photoluminescence, and electron spinresonance analyses. Oxygen vacancies accelerate the redox cycle between Ce₄+ and Ce₃+ by prolongingphotogenerated charge recombination. The ultrasound-treated pristine CeO₂ sample achieved excellenthydrogen production showing a quantum efficiency of 1.125% and efficient organic degradation. Ourpromising findings demonstrated that ultrasonic treatment causes the formation of surface oxygenvacancies and improves photocatalytic hydrogen evolution and pollution degradation. Conclusion: Defect engineering of the ceria nanoparticles with oxygen vacancies was achieved for the first time using low-frequency ultrasound treatment. The U-CeO₂₋ₓsample showed high crystallinity, and morphological changes were observed. Due to the acoustic cavitation effect, a larger surface area and small particle size were observed. The ultrasound treatment causes particle aggregation and surface defects leading to oxygen vacancy formation. The XPS, Raman spectroscopy, PL spectroscopy, and ESR results confirm the presence of oxygen vacancies. The ultrasound-treated sample was also examined for pollutant degradation, where 1O₂was found to be the major active species. Hence, the ultrasound treatment influences efficient photocatalysts for superior hydrogen evolution and an excellent photocatalytic degradation of contaminants. The prepared nanostructure showed excellent stability and recyclability. This work could pave the way for a unique post-synthesis strategy intended for efficient photocatalytic nanostructures.

Keywords: surface defect, CeO₂₋ₓ, photocatalytic, water treatment, H₂ production

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Authors: Sergejs Kolesovs, Pavels Semjonovs

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Whey and dairy wastewaters if disposed in the environment without proper treatment, cause serious environmental risks contributing to overall and particular environmental pollution and climate change. Biological treatment of wastewater is considered to be most eco-friendly approach, as compared to the chemical treatment methods. Research shows, that dairy wastewater can potentially be remediated by use of microalgae thussignificantly reducing the content of carbohydrates, P, N, K and other pollutants. Moreover, it has been shown, that use of dairy wastewaters results in higher microalgae biomass production. In recent decades microalgal biomass has entailed a big interest for its potential applications in pharmaceuticals, biomedicine, health supplementation, cosmetics, animal feed, plant protection, bioremediation and biofuels. It was shown, that lipids productivity on whey and dairy wastewater is higher as compared with standard cultivation media and occurred without the necessity of inducing specific stress conditions such as N starvation. Moreover, microalgae biomass production as usually associated with high production costs may benefit from perspective of both reasons – enhanced microalgae biomass or target substances productivity on cheap growth substrate and effective management of whey and dairy wastewaters, which issignificant for decrease of total production costs in both processes. Obviously, it became especially important when large volume and low cost industrial microalgal biomass production is anticipated for further use in agriculture of crops as plant growth stimulants, biopesticides soil fertilisers or remediating solutions. Environmental load of dairy wastewaters can be significantly decreased when microalgae are grown in coculture with other microorganisms. This enhances the utilisation of lactose, which is main C source in whey and dairy wastewaters when it is not metabolised easily by most microalgal species chosen. Our study showsthat certain microalgae strains can be used in treatment of residual sugars containing industrial wastewaters and decrease of their concentration thus approving that further extensive research on dairy wastewaters pre-treatment optionsfor effective cultivation of microalgae, carbon uptake and metabolism, strain selection and choice of coculture candidates is needed for further optimisation of the process.

Keywords: microalgae, whey, dairy wastewaters, sustainability, plant biostimulants

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Authors: Wei-Ru Chang, Jenn-Jiang Hwang, Zen-Ting Hsiao, Shu-Feng Lee

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Proton exchange membrane (PEM) fuel cells are widely used in electrical systems as an economical, low-polluting energy source. This study investigates the effects of PEMFC gas nitriding treatment on metal bipolar plates. The test material was SUS304 stainless steel. The study explored five different pretreatment processes, varying the corrosion resistance and electrical conductivity conditions. The most effective process was industrial acid washing, followed by heating to 500 °C. Under the condition, the corrosion current density was 8.695 μA, significantly lower than that of the untreated pretreatment sample flakes, which was measured as 38.351 μA.

Keywords: nitriding, bipolar, 304, corrosion, resistance, pretreatment

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Authors: Mwehe Mathenge, Ben G. J. S. Sonneveld, Jacqueline E. W. Broerse

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Smallholder farmers are important drivers of agriculture productivity, food security, and poverty reduction in Sub-Saharan Africa. However, they are faced with myriad challenges in their efforts at participating in agribusiness markets. How the geographic explicit factors existing at the local level interact to impede smallholder farmers' decision to participates (or not) in agribusiness markets is not well understood. Deconstructing the spatial complexity of the local environment could provide a deeper insight into how geographically explicit determinants promote or impede resource-poor smallholder farmers from participating in agribusiness. This paper’s objective was to identify, map, and analyze local spatial autocorrelation in factors that impede poor smallholders from participating in agribusiness markets. Data were collected using geocoded researcher-administered survey questionnaires from 392 households in Western Kenya. Three spatial statistics methods in geographic information system (GIS) were used to analyze data -Global Moran’s I, Cluster and Outliers Analysis (Anselin Local Moran’s I), and geographically weighted regression. The results of Global Moran’s I reveal the presence of spatial patterns in the dataset that was not caused by spatial randomness of data. Subsequently, Anselin Local Moran’s I result identified spatially and statistically significant local spatial clustering (hot spots and cold spots) in factors hindering smallholder participation. Finally, the geographically weighted regression results unearthed those specific geographic explicit factors impeding market participation in the study area. The results confirm that geographically explicit factors are indispensable in influencing the smallholder farming decisions, and policymakers should take cognizance of them. Additionally, this research demonstrated how geospatial explicit analysis conducted at the local level, using geographically disaggregated data, could help in identifying households and localities where the most impoverished and resource-poor smallholder households reside. In designing spatially targeted interventions, policymakers could benefit from geospatial analysis methods in understanding complex geographic factors and processes that interact to influence smallholder farmers' decision-making processes and choices.

Keywords: agribusiness markets, GIS, smallholder farmers, spatial statistics, disaggregated spatial data

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Authors: Sadaf Kalhori

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Introduction: Doxorubicin (DOX)-induced cardiotoxicity is widely known as the most severe complication of anthracycline-based chemotherapy in patients with cancer. It is unknown whether Deferiprone (DFP), could reduce the severity of DOX-induced cardiotoxicity by inhibiting free radical reactions. Thus, this study was performed to assess the protective effect of Deferiprone on DOX-induced cardiotoxicity in a rat model. Methods: The rats were divided into five groups. Group one was a control group. Group 2 was DOX (2 mg/kg/day, every other day for 12 days), and Group three to five which receiving DOX as in group 2 and DFP 75,100 and 150 mg/kg/day, for 19 days, respectively. DFP was starting 5 days prior to the first DOX injection and two days after the last DOX injection throughout the study. Electrocardiographic and hemodynamic studies, along with histopathological examination, were conducted. In addition, serum sample was taken and total cholesterol, Malone dialdehyde, triglyceride, albumin, AST, ALT, total protein, lactate dehydrogenase, total anti-oxidant and creatine kinase were assessed. Result: Our results showed the normal structure of endocardial, myocardial and pericardial in the control group. Pathologic data such as edema, hyperemia, bleeding, endocarditis, myocarditis and pericarditis, hyaline degeneration, cardiomyocyte necrosis, myofilament degeneration and nuclear chromatin changes were assessed in all groups. In the DOX group, all pathologic data was seen with mean grade of 2±1.25. In the DFP group with a dose of 75 and 100 mg, the mean grade was 1.41± 0.31 and 1±.23, respectively. In DFP group with a dose of 150, the pathologic data showed a milder change in comparison with other groups with e mean grade of 0.45 ±0.19. Most pathologic data in DFP groups showed significant changes in comparison with the DOX group (p < 0.001). Discussion: The results also showed that DFP treatment significantly improved DOX-induced heart damage, structural changes in the myocardium, and ventricular function. Our data confirm that DFP is protective against cardiovascular-related disorders induced by DOX. Clinical studies are needed to be involved to examine these findings in humans.

Keywords: cardiomyopathy, deferiprone, doxorubicin, rat

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Authors: Shailja Thakur

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In this paper it is shown that how farmers are suffering from all sides including vagaries of weather then price fluctuations, demand supply constraints, poor soil health etc. Also the ICT can prove to be of great help if incorporated rightly into Indian agriculture. Some innovative ways to reward farmers and distribution of subsidies to them can improve the current scenario.

Keywords: cost of farming, information and communication technology, innovative steps, roof gardening, vermicomposting

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Authors: Hsin-Yu Lin, Ching-Hsia Hung

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Obstructive sleep apnea (OSA) is characterized by a complete or partial obstruction of the upper airway during sleep. The vulnerable sites of upper airway collapses are consequences of sleep state-dependent reductions in tone in specific pharyngeal dilators. Clinical examinations reveal multilevel collapses of the upper airway among the patients with OSA. Therefore, an anatomically-based oropharyngeal rehabilitation should comprise a multilevel approach, including retropalatal, retroglossal, hypopharyngeal, temporomandibular, and facial levels, all of which involve different muscle groups and contribute to multifunctional interaction and coordination, such as swallowing, breathing, and phonation. The purpose of the study was to exam the effects of this rehabilitation program with a multilevel approach. In this study, fifteen subjects with newly diagnosed moderate or severe OSA (Apnea-Hypopnea-Index≥15) were randomized into an intervention group and control group. The intervention group (N=8) underwent a 12-week-intervention of a hospital-based rehabilitation program, while the control group (N=7) was kept on the waiting list. The 12-week-intervention comprised an anatomically based multilevel approach. The primary outcome was Polysomnography (PSG) data, and the secondary outcome was oropharyngeal and respiratory muscle function. In the intervention group, Apnea-Hypopnea-Index significantly improved (46.96±19.45 versus 32.78±10.78 events/h, p=0.017) compared with control group (35.77±17.49 versus 42.96±17.32 events/h, p=0.043). While the control group remained no change, the intervention group demonstrated other PSG outcomes significantly improvement, including arousal index (46.04±18.9 versus 32.98±8.35/h, p=0.035), mean SpO2 (92.88±2.1 versus 94.13±1.46%, p=0.039). Besides, the intervention group demonstrated significant improvement in oropharyngeal and respiratory muscle function compared to the control group. This anatomically-based oropharyngeal rehabilitation with a multilevel approach can be proven as a non-invasive therapy for patients with OSA.

Keywords: obstructive sleep apnea, upper airway, oropharyngeal rehabilitation, multilevel approach

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Authors: S. A. Nirmal, G. S. Asane, S. C. Pal, S. C. Mandal

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Objective: Ficus religiosa Linn (Moraceae) is being used in traditional medicine to improve immunity hence present work was undertaken to validate this use scientifically. Material and Methods: Dried, powdered bark of F. religiosa was extracted successively using petroleum ether and 70% ethanol in soxhlet extractor. The extracts obtained were screened for immunomodulatory activity by delayed type hypersensitivity (DTH), neutrophil adhesion test and cyclophosphamide-induced neutropenia in Swiss albino mice at the dose of 50 and 100 mg/kg, i.p. 70% ethanol extract showed significant immunostimulant activity hence subjected to column chromatography to produce tyrosine rich fraction (TRF). TRF obtained was screened for immunomodulatory activity by above methods at the dose of 10 mg/kg, i.p. Results: TRF showed potentiation of DTH response in terms of significant increase in the mean difference in foot-pad thickness and it significantly increased neutrophil adhesion to nylon fibers by 48.20%. Percentage reduction in total leukocyte count and neutrophil by TRF was found to be 43.85% and 18.72%, respectively. Conclusion: Immunostimulant activity of TRF was more pronounced and thus it has great potential as a source for natural health products.

Keywords: Ficus religiosa, immunomodulatory, cyclophosphamide, neutropenia

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Authors: Hamid Hatami

Abstract:

This experiment was included two cultivars i.e. Habbit and L17 (Main factor) with six fertilizer treatments i.e. control, seed inoculated with rhyzobium, base nitrogen + top-dress urea at R2 stage, base nitrogen + seed inoculated with rhyzobium + top-dress nitrogen at R2 stage, seed treated with humax + top-dress humax at R2 stage, base nitrogen + seed treated with humax + top-dress humax at R2 stage (sub factors ), as split-plot on the basis of RCBD with 3 replications at 2014. Treatment fertilizer of base nitrogen + seed treated with humax + top- dress humax at R2 stage and base nitrogen + top-dress urea in R2 stage had a significant superiority than the other fertilizer treatment in biological yield. L17 and Habbit with base nitrogen + seed treated with humax + top-dress humax in R2 stage and yield economical 5600 and 5767 kg/ha respectively, showed the most economical yield and Habbit cultivar with control and economical yield 3085 kg/ha showed the least economical yield among all the treatments. Results showed that fertilizer treatment of base nitrogen + seed treated with humax + top-dress humax in R2 stage and Habbit variety were suitable in this study.

Keywords: soybean, humax, rhyzobium, habbit

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Authors: Liang Ning, Chung Hau Yin

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Angiogenesis is the process of new blood vessel development. It has been recognized as a therapeutic target for blocking cancer growth four decades ago. Vascular sprouting is initiated by pro-angiogenic factors. Vascular endothelial cell growth factor (VEGF) plays a central role in angiogenic initiation, many patients with cancer or ocular neovascularization have been benefited from anti-VEGF therapy. Emerging approaches impacting in the later stages of vessel remodeling and maturation are expected to improve clinical efficacy. TIE receptor as well as the corresponding angiopoietin ligands, were identified as another endothelial cell specific receptor tyrosine kinase signaling system. Much efforts were made to reduce the activity of angiopoietin-TIE receptor axis. Two eudesmane-type sesquiterpenes from laggera alata, namely, 15-dihydrocostic acid and ilicic acid were found with strong anti-angiogenic properties in zebrafish model. Meanwhile, the mRNA expression levels of VEGFR2 and TIE2 pathway related genes were down-regulated in the sesquiterpenes treated zebrafish embryos. Besides, in human umbilical vein endothelial cells (HUVECs), the sesquiterpenes have the ability to inhibit VEGF-induced HUVECs proliferation and migration at non-toxic concentration. Moreover, angiopoietin-2 induced TIE2 phosphorylation was inhibited by the sesquiterpenes, the inhibitory effect was detected in angiopoietin-1 induced HUVECs proliferation as well. Thus, we hypothesized the anti-angiogenic activity of the compounds may via the inhibition of VEGF and TIE2 related pathways. How the compounds come into play as the pathways inhibitors need to be evaluated in the future.

Keywords: Laggera alata, eudesmane-type sesquiterpene, anti-angiogenesis, VEGF, angiopoietin, TIE2

Procedia PDF Downloads 205